tbuckley/cabot-search huggingface dataset:
Abstract 19153: In-Hospital Outcomes and Complications of Atrial Fibrillation Ablation: A Comparison Between Geriatric and Non-Geriatric Population
Authors: Olanrewaju Adabale, Olayiwola Bolaji, Faizal Ouedraogo, Revanth Reddy Bandaru, Maligireddy Anand Reddy, Akanimo Antia, Arnaud Yanogo, Stanley O Oghoghorie, Chukwuemezie Kamanu, Saeed Graham, Eric Chyn
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia associated with significant morbidity and mortality. The availability of different types of ablation for the treatment of AF is improved patient mortality and mitigate the disease burden. However, there is limited data on comparing post ablation results for AF in the geriatric population on geriatric population. Hypothesis: To study the in-hospital outcomes and complication of AF ablation among the geriatric and non-geriatric population groups. Methods: The National Inpatient Sampling from October 2016 to December 2019, a nationally representative sample of US hospitalizations. Adult (&gt;18 years) inpatient admissions with AF and ablation were identified based on International Classification of Diseases-Tenth Revision. The patient population is divided into three groups based on age i.e., group A (18-64 years), group B (65-74 years), group C (&gt;75 years). Results: A total of 15,800 AF patients over the age of 18 undergoing ABLA were identified. Among them, Group A accounted for 36.8%, Group B for 34.2%, and Group C for 28.9% of the patients. The female population in Group A was 28.7%, in Group B it was 40%, and in Group C it was 54.3% (p=0.03). Group C had higher prevalence rates of CHF (53.5%), COPD (22%), and CKD (30%) compared to the other groups (p&lt;0.000). When comparing Group C with Group A and B, patients in Group C experienced higher in-hospital mortality (0.8% vs 0.3% vs 0.4%; p&lt;0.000), cardiac complications (13.4% vs 5.9% vs 7.5%; p&lt;0.000), AKI (17% vs 11% vs 11.8%; p&lt;0.000), and major adverse events (MI or non-fatal stroke or CV death) (28.5% vs 16.9% vs 19.2%; p&lt;0.000). The rates of ICD/pacemaker implantation differed among Group A, B, and C (5.9% vs 10% vs 20.5%; p=0.000). Conclusions: Among AF patients undergoing ablation, those aged over 75 demonstrated higher rates of CHF, COPD, and CKD compared to other age groups. This population also experienced increased in-hospital mortality, cardiac complications, AKI, major adverse events (MI or non-fatal stroke or CV death), and had a significantly higher rate of ICD/pacemaker implantation. These findings emphasize the need for tailored interventions and closer monitoring for AF patients aged over 75 to improve outcomes.
Abstract 13861: Risk Prediction in Adults Late After Tetralogy of Fallot Repair: Does Machine Learning Provide Incremental Value Above Expert Clinical Judgement?
Authors: Ayako Ishikita, Chris McIntosh, Susan L Roche, David Barron, Erwin Oechslin, Lee N Benson, Krishnakumar Nair, Myunghyun M Lee, Kate A Hanneman, Gauri Rani Karur, Rachel M Wald
Journal: Circulation (2023)

Introduction and Aim: Machine learning (ML) can be used to predict major adverse cardiovascular events (MACE) in adults with repaired tetralogy of Fallot (rTOF). We sought to determine the incremental value of ML above expert clinical judgement for rTOF risk prediction. Methods: Adult congenital heart disease (ACHD) experts (≥10 years of clinical experience) participated (1 congenital heart surgeon and 4 cardiologists [2 with pediatric and 2 with adult cardiology training] with expertise in heart failure [HF], electrophysiology, imaging and intervention). Clinicians were individually asked to identify 10 high-yield clinical variables for 5-year MACE prediction (composite of mortality, resuscitated sudden death, sustained ventricular tachycardia and/or HF). Clinicians were blinded to outcomes and were asked to assign 5-year MACE risk (low, moderate, high) using 10 pre-specified variables for 25 adults with rTOF identified from an institutional database (prevalence of 5-year MACE 12%). A validated ML model was also used to predict outcomes in the same rTOF population using 10 variables. Results: Variables selected for risk prediction are shown (Figure A). As compared with the individual expert, the aggregate of 5 experts resulted in enhanced predictive capacity (Figure B). Predictive capacity of the ML model was similar to the aggregate of experts (Figures C,D). Experts with ≥20 years experience had better discriminative capacity for MACE prediction compared with &lt;20 years (AUC 0.98 [95%CI 0.86-0.99] versus 0.80 [95%CI 0.56-0.93], p=0.03). In those with &lt;20 years experience, ML provided incremental value such that the combined AUC approached ≥20 years (AUC 0.85 [95%CI 0.61-0.95], p=0.06). Conclusions: Prediction of 5-year MACE in rTOF using ML was similar to a multi-disciplinary team of ACHD experts. Risk prediction of less experienced clinicians was enhanced by incorporation of ML suggesting that there may be incremental value in select clinical settings.
Abstract 16919: Analysis of Astrocyte Activation and Reduction of Motor Deficits Following hSOX2 Gene Therapy Delivered Using PAMAM Dendrimer Nanomolecules in Ischemic Stroke
Authors: Bhairavi Srinageshwar, Justin Stadler, Melissa Andrews, Bethany MacDonald, Alexa Toth, Arjun Poudel, Raegan Schalau, Clayton Malkowski, Harrison Schurr, Joseph Hellrung, Douglas Swanson, Ajit Sharma, Gary Dunbar, Julien Rossignol
Journal: Circulation (2023)

PAMAM dendrimers are 3-dimensional nanomolecules which have the capability to deliverbiomolecules and gene therapy to the cells in vitro and in vivo . We have previously used the generation-4 surface-modified PAMAM dendrimers having 90% hydroxyl groups and 10% amine groups (G4-90/10) which are safe, cross the blood-brain barrier and deliver the biomolecules into the cells. In thecurrent study, we utilized G4-90/10 PAMAM dendrimers to deliver a gene therapy to the infarct in aischemic stroke brain in rats. Following an ischemic stroke, glial cells (such as astrocytes) are recruitedat the infarct region to perform maintenance functions, creating severe neuroinflammation. The goalof this study was to reprogram some of the astrocytes into neuronal lineage and repopulate the infarctregion. In addition, we also analyzed the temporal profile of astrocyte activation following ischemicstroke in the striatal and cortical regions to determine the time-point at which the maximum gliosisoccurs. This gives us a crucial timeline for treatment intervention to achieve astrocytereprogramming. We have used a transcription factor (hSOX2 gene), which was then delivered to thestroke brain in rats using the G4-90/10 dendrimers. Our results showed that the maximum glial cellactivation occurs in striatal and cortical regions on day 4 following ischemic stroke. Following genetherapy intervention, our initial analyses indicated that there was recovery from behavioral deficits inthe stroked rats compared to the vehicle-treated stroked rats and sham controls. Overall, these resultsshow that PAMAM dendrimers have significant potential delivering therapeutic molecules for treatingstroke and other neurological conditions. Support for this study was provided by the American Heart Association (18AIREA 33990094),Neuroscience program, the College of Medicine, department of Chemistry and Biochemistry, the JohnG. Kulhavi Professorship and the E. Malcolm Field and Gary Leo Dunbar Endowed Chair of Neuroscience at Central Michigan University.
Abstract 12577: Sex Differences in Outcomes of Percutaneous Coronary Intervention for Stable Coronary Artery Disease in Patients With End Stage Kidney Disease
Authors: Ahmad Mahdi, Harsh Mehta, Wan Chi Chan, Rhythm Vasudeva, Mohinder Reddy Vindhyal, Caroline Trupp, Amelia Greene, Kartik Munshi, Peter Tadros, PRASAD GUNASEKARAN, Sania Jiwani, CYRUS MUNGUTI, Gokul Ramani, Georges Hajj, Mark Wiley, Eric Hockstad, Kamal gupta
Journal: Circulation (2023)

Introduction: End Stage Kidney Disease (ESKD) patients are at a higher risk of morbidity and mortality from cardiovascular diseases, particularly coronary artery disease (CAD). There is paucity of sex related differences in percutaneous coronary intervention (PCI) outcomes in this population. Methods: Patients ≥ 18 years with ESKD on dialysis for at least 3 months and who underwent PCI for stable CAD between years 2010 and 2018 were identified from the United States Renal Data System (USRDS) database. Appropriate ICD-9/10 codes were used to identify the relevant conditions and procedures. Statistical analyses were performed using the SAS 9.4 software. Results: A total 23,115 ESKD patients underwent PCI, of which 42.5% were women. While there was a declining trend of utilization of PCI (Men: 6.6 to 2.8; Women: 6.6 to 2.7 procedures per thousand ESRD patients; p&lt;0.001), the in-hospital mortality (Men:1% to 3.2%, p&lt;0.001; Women:0.7% to 2.8%, p&lt;0.001), 30-day mortality (Men:3% to 6.8%, p&lt;0.001; Women:3.5% to 5.2%, p&lt;0.001) and 1-year mortality (Men: 25.6% to 32.7%, p&lt;0.001; Women: 27.7% to 30.4%, p&lt;0.001) as well as 30-day myocardial infarction (Men: 2.7% to 4%,p&lt;0.001; Women:3.1% to 5.6%, p&lt;0.001) increased in both sexes during the study period. After propensity matching, hospital length of stay (3 days vs 4 days, p&lt;0.001), 30-day readmission (29.4% vs 33.1%, p&lt;0.001) and 1-year incidence of stroke (2.3% vs 3.3%, p&lt;0.001) were higher in women, while other outcomes were not significantly different between men and women. Conclusions: Despite the decreasing utilization of PCI for stable CAD in ESKD patients over the study period, worsening short- and long-term mortality was observed in both sexes. Women were more likely to have a longer hospital stay as well as readmission within 30 days post-procedure.
Abstract 12528: DNA Methylation Profiles of 3 Major CHIP Subtypes Provide Insight Into Underlying Epigenetic Mechanisms
Authors: Sara Kirmani, Tianxiao Huan, Roby Joehanes, Chunyu Liu, Jiantao Ma, Alexander G Bick, Nancy Heard-Costa, Joanne Murabito, Daniel Levy
Journal: Circulation (2023)

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related phenomenon characterized by the presence of clonal populations of hematopoietic-derived cells in whole blood that harbor functional leukemogenic somatic mutations. Despite the well-established associations between aging and CHIP and aging and genome-wide DNA methylation (DNAm), the association between CHIP and changes in DNAm remains to be fully elucidated. To fill this knowledge gap, an epigenome-wide association study of CHIP was performed in Framingham Heart Study participants from the Offspring cohort (n total = 1594; 54% women; mean age 67 years) using whole blood derived DNA to elucidate the DNAm profiles of any CHIP and the three most frequently mutated CHIP driver genes DNMT3A, TET2 , and ASXL1/2 . Linear mixed models were used to test associations between CHIP status as the predictor variable and genome-wide DNAm of CpG sites as the outcome, with adjustment for age, age 2 , sex, smoking, 33 surrogate variables, and familial relatedness. From the analysis, 189 CpGs were found to be associated with any CHIP, and 139, 107, and 4 were associated with DNMT3A , TET2 , and ASXL1/2 CHIP, respectively (Bonferroni corrected P&lt;1х10 -7 ). The CpGs associated with the DNMT3A , TET2 , and ASXL1/2 CHIP were distinct. Genome-wide DNAm directions of effect were similar for DNMT3A and ASXL1/2 CHIP but opposite to TET2 . Gene expression analysis identified CpG-gene transcript pairs for any CHIP and CHIP subtypes. The most significant gene sets were enriched in pathways related to immune response and hematopoietic cell lineage. Two-sample Mendelian randomization analysis was additionally conducted to investigate whether methylation at CHIP-associated CpGs causally influences risk of cardiometabolic traits and all-cause mortality. Evidence of a putative causal role of CHIP-associated CpGs in relation to several traits, including BMI and hypertension, and all-cause mortality was found. Taken together, we identified CpGs associated with CHIP and with the three major CHIP driver genes, elucidated their methylomic signatures, identified CpG-transcript pairs, and provided support for a potential causal role of CHIP-associated CpGs in relation to cardiometabolic traits and all-cause mortality.
Abstract 13867: Sustained Improvement in Door-to-Balloon Time Over 15 Years: The Aurora St. Luke’s 24x7 STEMI Program With Redefinition of Contemporary Door-to-Balloon Time Less Than 60 Minutes: 60 is the New 90
Authors: Muddasir Ashraf, Suhail Q Allaqaband, Tanvir Bajwa, Sara Walczak, Kirsten Tunink, Michael Peterson, Christopher Koblosky, M F Jan
Journal: Circulation (2023)

Background: In April 2004, Aurora St. Luke’s Medical Center implemented an in-house 24x7 interventional cardiology program to improve door-to-balloon time (D2BT) in ST-segment elevation myocardial infarction (STEMI). Previously published data showed a significant reduction in median D2BT, from 98 minutes (January 1, 2002-March 31, 2004) to 55 minutes (April 1, 2004-June 30, 2008), along with a reduction in major adverse cardiovascular events (MACE) and mortality after implementation of the program. Hypothesis: We hypothesized that the continued experience with the 24x7 program would demonstrate further gain in STEMI outcomes in regard to D2BT. Aims: The primary objective was to evaluate the overall median D2BT over a 15-year period. The secondary objectives were to evaluate median D2BT stratified by weekdays and weekends, on- and off-hours, the proportion of D2BT &lt;90 minutes, and the proportion of D2BT &lt;60 minutes over time. Methods: We collected data on all non-transfer adult patients with STEMI from April 1, 2004, to March 31, 2019, at our center. On-hours were from 7:30 a.m. to 5 p.m. and off-hours from 5 p.m. to 7:30 a.m. Results: A total of 1889 patients with STEMI (median age [IQR] 61 [54-71] years, 31% female) were evaluated. Over 15 years, median D2BT decreased from 69 minutes to 46 minutes (P &lt; .001; Fig 1A). The decreasing trend was seen on weekdays and weekends (Fig 1B) and on-hours and off-hours. The percentage of cases with a median D2BT &lt;90 minutes increased from 77% to 97% over 15 years, and those with a median D2BT &lt;60 minutes increased from 36% to 76% (Fig 1B). Conclusion: We show sustained improvement in our median D2BT and remarkable improvement in the proportion of D2BT &lt;60 minutes. This paves the way for redefining the contemporary D2BT from &lt;90 to &lt;60 minutes.
Abstract 12552: Unmasking Unstable Angina: The Crucial Influence of Chest Pain Perception in Hospital Management Strategies
Authors: Mateus A Prata, Louis N Ohe, Kelvin H Vilalva, Lucas Lemos, Diandro M Mota, PAOLA E SMANIO
Journal: Circulation (2023)

Introduction: Managing unstable angina (UA) poses a significant challenge due to its subjective diagnosis and underrepresentation in pivotal clinical trials that have greatly influenced current practices. The aim of this study is to determine the key variables that impact the management of UA in a referral cardiology hospital. Hypothesis: In addition to prognostic scores, other factors such as the nature of chest pain may have a relevant role in the management of UA. Methods: This retrospective cohort study enrolled patients consecutive hospitalized with a diagnosis of UA from July 16, 2018 to February 28, 2020. The primary objective was to analyze the factors associated with the utilization of either an invasive or non-invasive strategy. The secondary objective sought to identify the factors associated with the presence of obstructive coronary artery disease (CAD) or ischemia, as determined by the results of complementary tests. Between-group comparisons were performed using multiple logistic regression analysis, with statistical significance set at a 5% level. Results: A total of 729 patients were included in the study, with a mean age of 62.9 years, with a male predominance (64.6%). Factors significantly associated with an invasive strategy were smoking (p = 0.001), type of chest pain (p &lt; 0.001), angina "in crescendo" (p = 0.006), TIMI risk (p = 0.006), and HEART score (p = 0.011). In the multivariate analysis, current smokers (OR 2.23, CI 95% 1.13-4.8) and type A chest pain (OR 3.39, CI 95% 1.93-6.66) were independently associated with the invasive strategy. Regarding the presence of obstructive CAD or ischemia, male gender (p = 0.032), exertional chest pain (p = 0.037), Diamond-Forrester (p = 0.026) and TIMI risk (p = 0.001) showed significant associations. In the multivariate analysis, the type of chest pain (type B chest pain: OR 0.6, CI 95% 0.38-0.93, p = 0.026) and presence of previous CAD (OR 1.42, CI 95% 1.01-2.0, p = 0.048) were independently associated with obstructive CAD or ischemia. Conclusion: Chest pain type is not only instrumental in diagnosing UA but also critical in shaping the suitable treatment approach. Our study emphasizes the significance of integrating pain traits with guidelines-endorsed scoring systems for optimal management.
Abstract 16084: Impairment of Cardio-Spleno-Bone Marrow Axis Following Myocardial Infarction in Diabetes Mellitus
Authors: Amankeldi A Salybekov, Mehdi Hassanpour, Kanat Tashov, Ainur Salybekova, Yin Sheng, Yoshiko Shinozaki, Shuzo Kobayashi, Takayuki Asahara
Journal: Circulation (2023)

Introduction: Precise comprehension of the cardio-spleen-bone-marrow immune cells axis is crucial to understanding the changes occurring during diabetes (DM) pathogenesis. This study aims to investigate the alterations in immune cell kinetics in DM after myocardial infarction (MI). Methods: MI was induced in DM and healthy control using C57BL/N6 mice. Animals were sacrificed at D1, D3, D7, &amp; D28 post-MI to obtain their heart, peripheral blood (PB), spleen, and bone marrow (BM) and then each organ cell suspension was isolated, and analyzed by flow cytometry. EPC-colony-forming assay (EPC-CFA) was performed using BM, PB, and spleen-derived MNCs. Results: Findings demonstrated that despite the normal production of BM, CD45+ cells are decreased at D1-D3 in spleen and PB of DM’s. Further analysis depicted that total and pro-inflammatory neutrophil (N1) decreased at D1-D3 in PB and spleen at D3-D7 in DM mice, suggesting that DM causes spleen's neutrophil alterations that cannot compensate for PB and ischemia tissue demand. Infiltrated macrophages (total, M1, M2) decreased at D3 in DM-ischemic heart. Total and M1 (D1-D3) and M2 (D3-D7) notably decreased in DM-PB than control group, showing impaired macrophage recruitment/polarization in DM. Moreover, heart myeloid dendritic cells (mDCs) increased from D1-D7, the latter enhanced recruitment of CD8 cells increase from D1 to D28 in DM-infarcted-myocardium. The total CD4 cells decreased at D1-D3 in DM-PB, indicating a delayed adaptive immune response to MI. The B-cells diminished at D1-D3 in PB, at D3 in myocardium, and D7 in spleen, indicating impaired mobilization of those cells from bone marrow to compensate. EPC-CFA demonstrated dramatically decrease of definitive EPC colonies in spleen and BM from D1-D28 in DM mice vs control in vitro , indicating that DM significantly impairs EPC colony-forming bioactivity by limiting EPCs' differentiation from primitive to definitive. Conclusion: Our study highlights significant alterations of cardio-spleno-bone-marrow immune cells axis following MI in DM animals, revealing delayed innate/adaptive immune responses and impaired differentiation of EPCs.
Abstract 19124: Systemic Sclerosis Masquerading as Heart Failure
Authors: Sruti Prathivadhi-Bhayankaram, Shareef Mansour
Journal: Circulation (2023)

Cardiac disease occurs in 80% of patients with systemic sclerosis (SS). Patients may present with various symptoms, including dyspnea, palpitations, chest pain, and heart failure. Of these, systolic heart failure has the rarest prevalence, estimated between 1-5% of patients. The mechanism behind myocardial damage is still unclear. Current literature supports a fibrotic process due to ischemic necrosis and reperfusion damage. There is a lack of representation of SS-related cardiac disease, but it is crucial to recognize it early for prompt intervention. A 62-year-old male with a history of diastolic dysfunction presented with acute hypoxic respiratory failure. A transthoracic echocardiogram demonstrated a new severely reduced systolic function at 20%. Angiogram demonstrated non-obstructive coronary artery disease. Further autoimmune workup revealed a significantly elevated ANA and highly positive RNA polymerase III antibody. The patient underwent a cardiac magnetic resonance imaging (MRI) scan, which showed evidence of inflammation with diffuse myocardial fibrosis concerning an infiltrative process. Subsequent cardiac positron emission tomography (PET) showed increased uptake in the basal portions of the septum and anterior wall for myocarditis. Given his autoimmune workup results and imaging, the patient was subsequently diagnosed with rapidly progressive cutaneous systemic sclerosis and associated non-ischemic cardiomyopathy. The patient was started on goal-directed medical therapy, including losartan, spironolactone, metoprolol, and empagliflozin. Additionally, he started on mycophenolate mofetil for immunosuppression. Roughly six months after discharge, his pulmonary function tests remain stable. His ejection fraction improved to 62%. Roughly one-third of systemic sclerosis-related deaths are due to cardiac involvement. Yet, most patients are asymptomatic during the early stages, with a variable phenotype later in disease progression. We report a case of a patient who developed systemic sclerosis-related myocarditis with an initial presentation of acute systolic heart failure. His cardiac dysfunction recovered from optimal goal-directed therapy and immunosuppression.
Abstract 19137: Chronic Kidney Disease is an Important Predictor of 2-Year Mortality After Chronic Limb Ischemia Repair Using Either Endovascular or Bypass Graft Intervention
Authors: Angela Wang, Antonio Solano, Richard Tyler Miller, Carlos H Timaran, J. Gregory Modrall, Shirling Tsai, Melissa L Kirkwood, Bala Ramanan
Journal: Circulation (2023)

Introduction: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with worse outcomes after both endovascular (PVI) and bypass graft intervention (OI) of critical limb ischemia (CLI). Research Question: Do surgical outcomes of CLI repair differ by approach and CKD severity? Methods: Patients undergoing elective CLI intervention with preoperative renal function data captured by the Vascular Quality Initiative between Jan 2003 and Dec 2018 were analyzed. Patients were stratified by CKD class: normal/mild (CKD stage 1-2), moderate (CKD stage 3a), moderate-severe (CKD stage 3b), severe (CKD stage 4-5), and dialysis. Primary outcomes were 30-day, 1-year, and 2-year mortality, and incidence of major amputation. Predictors of survival were identified by Cox multivariate regression. Results: Out of 18,399 patients who underwent elective CLI treatment, 13,366 had PVI and 5033 had OI. Table 1 demonstrates the distribution of patients and primary outcomes. On Kaplan Meier analysis, 2-year survival favored the normal/moderate CKD cohort after both PVI and OI. On Cox regression analysis, when compared to normal/ mild CKD, CKD Class 3b (HR 1.405, p&lt;0.001) and Class 4 (HR 1.712, p&lt;0.001), and Class 5 (HR, 1.649, p = 0.070) were associated with worse 2-year mortality after OI. When compared to normal/mild CKD, CKD Class 3b (HR, 1.427 [1.2-1.7], p&lt;0.001), Class 4 (HR, 2.256 [1.77-2.87], p&lt;0.001), and Class 5 (HR, 1.210 [.59-2.5], p = 0.603) were associated with worse 2-year mortality. 2-year amputation rates did not demonstrate statistically significant differences among CKD classes. Conclusion: CKD severity is an important predictor of 2-year mortality after CLI repair regardless of approach but does not predict 2-year major amputation rates. Overall, PVI is associated with lower mortality and major amputation.